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Aberrant DNA methylation in ES cells

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Item Type:Article
Title:Aberrant DNA methylation in ES cells
Creators Name:Ludwig, G. and Nejman, D. and Hecht, M. and Orlanski, S. and Abu-Remaileh, M. and Yanuka, O. and Sandler, O. and Marx, A. and Roberts, D. and Benvenisty, N. and Bergman, Y. and Mendelsohn, M. and Cedar, H.
Abstract:Both mouse and human embryonic stem cells can be differentiated in vitro to produce a variety of somatic cell types. Using a new developmental tracing approach, we show that these cells are subject to massive aberrant CpG island de novo methylation that is exacerbated by differentiation in vitro. Bioinformatics analysis indicates that there are two distinct forms of abnormal de novo methylation, global as opposed to targeted, and in each case the resulting pattern is determined by molecular rules correlated with local pre-existing histone modification profiles. Since much of the abnormal methylation generated in vitro appears to be stably maintained, this modification may inhibit normal differentiation and could predispose to cancer if cells are used for replacement therapy. Excess CpG island methylation is also observed in normal placenta, suggesting that this process may be governed by an inherent program.
Keywords:Cell Differentiation, Cell Line, CpG Islands, DNA Methylation, Embryonic Stem Cells, Genetic Epigenesis, Inbred C57BL Mice, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:9
Number:5
Page Range:e96090
Date:22 May 2014
Official Publication:https://doi.org/10.1371/journal.pone.0096090
PubMed:View item in PubMed

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